THE USE OF ALFUZOSIN OR TERAZOSIN IN THE TREATMENT OF PREMATURE EJACULATION

Abstract: The use of the a1-blockers drugs, alfuzosin and terazosin in the treatment of premature ejaculation is disclosed.

Description: THE USE OF ALFUZOSIN IN THE TREATMENT OF PREMATURE EJACULATION The present invention relates to the use of αl blockers in the treatment of premature ejaculation. Primitive psychogenic premature ejaculation is regarded as the most common sexual disorder of the male. At present, the treatment of choice is psychotherapy, either as a behavioural dual team sex therapy according to Master & Johnson protocol, or individual psychotherapy (Rifelli and Moro. Sessuologia Clinica. Bologna, 1989). The first proved to be active in about 80% of the cases, and it needs an active couple with a strong background of conjugal life free from conflictualities, while the second proved to be active in 40%-60% of the cases (1). This means that a large amount of males do not benefit from the psychotherapy and still suffer from premature ejaculation. Ejaculation is a centrally integrated peripheral evoked reflex, which occurs thanks to an αl adrenergic receptor activation. Effective pharmacological drugs for the treatment of premature ejaculation exist, but they suffer from severe side effects, for example clomipramine and phenoxybenzamine . Other treatments have a limited effectiveness (metoclopramide and the like). Now it has been found that two specific αl blockers, alfuzosine and terazosine, are effective in the treatment of psychogenic premature ejaculation. Particularly, said drugs turned out to be effective in patients who proved to have no benefit from psychological therapy. Therefore, it is an object of the present invention the use of alfuzosine and terazosine and the pharmaceutically acceptable salts thereof for the preparation of a medicament useful for the treatment of psychogenic premature ejaculation. Alfuzosine and terazosine are αl blockers used in jυ the treatment of hypertension or in the symptomatic treatment of benign prostatic hyperplasia. Up to now no paper can be found in literature about any possible use thereof in the treatment of psychogenic premature ejaculation, particularly in patients resistant to I.-.-- psychotherapy. In the following, the clinical evaluation of alfuzosine and terazosine is illustrated. 107 Patients complaining psychogenic premature ejaculation were tested during 2 years. Age range was V'J 21-63 years, mean age 34.3 years: all of them were put into a blind cross-over prospective controlled trial. Alfuzosine, terazosine and placebo (vitamin C) were used. Criteria for the participation in the study were absence of: uncontrolled hypertension, orthostatic hypotension, thyroid- diseases..,, uncontrolled diabetes, recent miocardial infarction, use of alfuzosine or of terazosine in the previous 4 months, sexual life characterised by occasional intercourses. . -■() The patients were randomized in three groups: two of 36 and one of 35 patients. Each group used alfuzosine, terazosine or placebo in a different order. The first group used the drugs as follows: alfuzosine, terazosine, placebo; the second group used first terazosine, followed by placebo and alfuzosine; the third group used first placebo, then alfuzosine and finally terazosine. Each drug was used during two months. Alfuzosine dosage was 2x3 mg/day, terazosine 5 mg/day once a day (the dosage was gradually reached starting from 1 mg/day) and vitamin C 500x2 mg/day. in six patients dropped out from the study for unknown causes, and 4 patients had to be discharged from the study due to the side effects of the drugs. At the end of each two-month period of treatment, the patients and their partners were separately asked ι r > wether or not they were satisfacted by the activity of the drugs: i.e. wether or not time required to reach ejaculation had been prolonged enough to be satisfactory for both. In 6 cases a disagreement about the times of orgasmic latency was evidenced between so patients and their partners and therefore these were discharged from the study. At the end of the study, 91 cases were evaluated, which were subdivided into a first group of 30 patients, a second of 30 and a third of 31. Results were categorized as follows: positive (satisfactory for both partners.) or negative (unsatisfactory for both, partners). Data were analyzed with the chi square test. The results are listed in the following tables. Table 1 shows the activity of the drugs: -J" alfuzosine proved to be active in 42 patients (46.2%), terazosine in 48 (53,7%) and placebo in 22 (24,2%). Table 1 Effect of αl-blockers in the treatment of premature ejaculation psychogenic I group alfuzosine terazosine placebo positive results 14 (46.7%) 16 (53.3%) 8 (26.7%) negative results 16 (53.3%) 14 (46.7%) 22 (73.3%) TOTAL 30 30 30 II group terazosine placebo alfuzosine positive results 15 (50.0%) 10 (33.3%) 13 (43.3%) o negative results 15 (50.0%) 20 (66.7%) 17 (56.7%) TOTAL 30 30 30 III group placebo alfuzosine terazosine positive results 4 (12.9%) 16 (51.6%) 17 (54.8%) negative results 27 (87.1%) 15 (48.4%) 14 (45.2%) TOTAL 31 31 31 The results prove that alfuzosine and terazosine are significantly more active than placebo (chi square 8.70, p<0.05 and 14.50, p<0.01 respectively) whereas non significant differences were evidenced between 0 alfuzosine and terazosine (chi square 0.55, p not significant). When placebo was used as first (III group), this turned out to be active for 12.9% of cases,; on the other hand, when used after the α- blocker, it proved effective in about 30% of cases, a trend which, even though suggestive, is not significant (chi square 2.55). Table 2 shows side-effects. The 4 patients who had been discharged from the clinical evaluation were also considered. ,0 Table 2 Side effects induced by the treatment with alfuzosine, terazosine and placebo. Appearance of No side effects side effects Alfuzosine 5~ (5.2%) 90 (94.8%) Terazosine 3* (3.2%) 90 (96.7%) Placebo 1+ (1.1%) 90 (98.9%) 3 patients reported hypotension (2 patients of group 1 interrupted the treatment and received no terazosine), 1 hypotension and epigastralgia, 1 epigastralgia. * 2 patients of group 2 reported hypotension, interrupted the treatment and received no placebo, 1 reported headache. + 1 patient reported slight epigastralgia. The results of clinical evaluation prove that αl- blockers alfuzosine and terazosine are effective in the treatment of psychogenic premature ejaculation, particularly in patients resistant to psychotherapy. The use of said drugs proved to be safe from the side effects point of view. The dosage will be determined by the physician depending on the severity of the pathology and the general conditions of the patient. Generally, dosages from 1 to 8 mg/day for alfuzosine and from 3 to 15 mg/day for terazosine can be envisaged", possibly subdivided into more- daily doses. According to another object of the invention, alfuzosine and terazosine can also be used in combination in the same medicament, or in combination with one or more compounds effective in the treatment of premature ' ejaculation, such as antiandrogens, metoclopramide, clomipramine, phenoxybenzamine, prazosine and lorazepam. The preferred administration route is the oral one, but other administration routes can also be envisaged. According to the invention, the drugs herein described will be administered in form of pharmaceutical compositions which can be prepared 10 according to conventional procedures, for example as described in Remington's Pharmaceutical Sciences Handbook, XVII ed, Mack, Pub., USA. Examples of pharmaceutical compositions are tablets, capsules sugar-coated pills, syrups, chewable J ^ formulations; suppositories and injectable formulations (intravenous, subcutaneous, intramuscular).

Claims: CLAIMS 1. The use of alfuzosine and the pharmaceutically acceptable salts thereof for the preparation of a medicament for the treatment of psychogenic premature ejaculation. 2. The use of terazosine and the pharmaceutically acceptable salts thereof for the preparation of a medicament for the treatment of psychogenic premature 10 ejaculation. 3. The use of alfuzosine and the pharmaceutically acceptable salts thereof in combination with one or more compounds selected from antiandrogens, metoclopramide, clomipramine, phenoxybenzamine, J 5 prazosine and lorazepam for the preparation of a medicament for the treatment of psychogenic premature ejaculation. 4. The use of terazosine and the pharmaceutically acceptable salts thereof in combination with one or 2d more compounds selected from antiandrogens, metoclopramide, clomipramine, phenoxybenzamine, prazosine and lorazepam for the preparation of a medicament for the treatment of psychogenic premature ejaculation.

Inventors: CAVALLINI GIORGIO, CAVALLINI, GIORGIO
Applicants: CAVALLINI GIORGIO, CAVALLINI, GIORGIO
Application year: 1994
Main classification: A61K31
IPC codes: A61K31, A61K45, A61P13, A61P15, A61P43, C07D405